丙戊酸钠对重度烫伤大鼠心肌保护作用及其机制研究  

Protective effect and its mechanism of valproic acid sodium salt on heart with severe scald in rats

作　　者：白慧颖[1] 周国勇[1] 张立俭[1] 胡森[1] 

机构地区：[1]解放军总医院第一附属医院烧伤研究所休克与多器官障碍实验室,北京100048

出　　处：《中国临床药理学杂志》2011年第2期130-132,145,共4页The Chinese Journal of Clinical Pharmacology

基　　金：全军医学科研"十一五"专项课题基金资助项目(06Z055)

摘　　要：目的研究丙戊酸钠(抗癫痫药)对重度烫伤大鼠心肌保护作用及其机制。方法 98只♂SD大鼠,随机分为4组:①假烫组、②烫伤组、③烫伤+二甲基二乙酸(2M2P)组和④烫伤+丙戊酸钠(VPA)组,80℃水浴(假烫组37℃),造成50%总体表面积(TBSA)Ⅲ度烫伤。③、④组分别于烫伤后,即刻皮下注射2M2P、VPA300 mg.kg-1。分别于烫伤后2,6 h腹主动脉取血,测定磷酸肌酸激酶同工酶(CK-MB)变化;然后处死大鼠观察心肌病理变化;检测心肌热休克蛋白(HSP70)表达。结果烫伤大鼠血浆CK-MB水平持续升高,于伤后6 h,VPA组的血浆CK-MB水平(U.L-1)显著低于烫伤组(4398.0±1273.8 vs5438.0±987.9,P<0.01)和2M2P组(4398.0±1273.8 vs 5198.0±1097.3,P<0.01),HSP70表达明显高于烫伤组和2M2P组。病理观察显示,VPA组的心肌损伤轻于烫伤组和2M2P组。结论 VPA改善烫伤休克大鼠心肌酶学指标和组织学损伤,其机制可能与其促进保护性蛋白HSP70表达增多有关。Objective To investigate whether administration of VPA after lethal scalded,without fluid resuscitation,would protect against heart damage and its mechanism.Methods Ninety-eight male Sprague-Dawley（SD） rats were randomized divided into four groups：① no lethal scalded,②lethal scalded with no resuscitation,③lethal scalded with 2-methyl-2-pentenoic acid（2M2P） and ④ lethal scalded with valproic aicd（VPA）.In the first experiment,rats were subjected to 50% total body surface area（TBSA） full-thickness flame injury.After this process,blood samples were taken by ventral aorta at 2 hours,6 hours for the measurement of MB isoenzyme of creatine kinase（CK-MB）.Animals were sacrificed at the end of experiment.Heart tissues were used for immunohistochemical（IHC） analysis HSP70.Results The increase in CK-MB levels after burn shock was lower in the VPA group,suggesting heart protection.The levels of HSP70 in cardiac tissue from the VPA group were significantly higher than the animals with burn shock without VPA pretreatment.Conclusion VPA offers considerable protection in lethal scalded.We found that the expression of HSP70,implicated in the modulation of vitality,was increased by VPA.The role of HDAC inhibition and protective protein are suggested in mediating prosurvival actions of VPA.

关 键 词：烫伤 组蛋白去乙酰化 热休克蛋白 丙戊酸钠 

分 类 号：R965[医药卫生—药理学] R971.6[医药卫生—药学]